This K08 proposal describes a 5-year training program for the development of an academic career in addiction research. The candidate completed his M.D. and Ph.D. in Neuroscience, and then went on to complete a structured residency in Psychiatry at the University of Michigan. He was recently appointed Assistant Professor of Psychiatry at University of Michigan, where in addition to basic research he now treats patients with substance use disorders at the Addiction Treatment Services clinic. The candidate's education and training in both neuroscience and psychiatry have prepared him well for this project, and he will now expand on his scientific skills through a unique integration of interdepartmental resources. To achieve full research independence, he has identified three key Training Objectives: (1) to gain proficiency in advanced neuroanatomical techniques, particularly immunohistochemistry, (2) to gain expertise in microinjections and the use of viral vectors to experimentally manipulate behavior, and (3) to learn how to use optogenetics as a tool for interrogating neural circuits that influence specific behaviors. The proposed K08 project will take place within the Department of Psychiatry and the Molecular & Behavioral Neuroscience Institute at the University of Michigan. The Department and Institute benefit from close collaborative relationships with other units including Bioengineering, Psychology, Radiology, and the CTSA- funded Michigan Institute for Clinical and Health Research. This vigorous research environment includes ample access to behavioral testing facilities, histology and microscopy resources, and animal housing, and it nurtures an expanding group of translational psychiatric researchers. The primary mentor, Terry Robinson PhD, is a productive and well-funded neuroscientist who has more than 30 years of experience with basic addiction research, and an established track record of mentoring junior investigators. The candidate will also benefit from two local co-mentors, Stanley Watson MD PhD, who pioneered the use of immunohistochemistry to study emotional behavior and has mentored several successful physician-scientists over his 30+ years of research, and Gina Poe PhD, an Associate Professor of Anesthesiology who has expertise in the use of optogenetics to study behavior in rats. Pedro Lowenstein MD PhD is an experienced consultant on this project with considerable expertise in viral vectors and translational research. The research project focuses on identifying common neurobiological substrates that confer vulnerability both to addiction and to frequently co-occurring disorders such as post-traumatic stress disorder. This will be accomplished by identifying neural circuits responsible for generating excessive emotional and motivational responses to both appetitive and aversive conditioned cues. The specific aims include: 1) identifying areas of overlap in the neurons and circuits activated by both appetitive and aversive conditioned cues, 2) testing whether increasing connectivity within limbic circuitry can simultaneously reduce both conditioned approach and conditioned fear, and 3) using optogenetics to identify specific pathways that exert inhibitory control over both appetitive and aversive motivational responses. The proposed K08 project is well-aligned with the missions of the NIH and NIDA. The project will train a promising scientist and help clarify neurobiological pathways to addiction and frequently co-occurring disorders, which is a significant public health priority.